About Trefoil Factor:

There are 3 trefoil factors, coded as TFF1-3, and they’re a group of closely linked peptides. Though each one will play a slightly different role, their main overall purpose is to assist in with the repair and protection of epithelial surfaces. Each TFF protein is always present in the gastrointestinal tract, meaning they exist in almost every mucous membrane throughout the body.

Mechanism/InteractionsAll of the trefoil factors are products secreted by mucin cells. They’re produced by goblet cells and are part of the immune response to help defend the layer of mucosa on the epithelium. It is well known and talked about how important TFFs are in protecting and repairing epithelial surfaces. These peptides are known to be resistant to things such as acids, thermal degradation, and proteolytic digestion. This is thought to be because of how their structure is formed, in a compact trefoil shape. TFF2 is mainly produced in the neck cells and antral glands of the stomach. TFF1 is found in the stomach as well, only this peptide is produced by superficial gastric foveolar cells. TFF3 is primarily secreted by the goblet cells found in both intestines.

FunctionAll of the trefoil factors are characterised as such due to the appearance of at least one version of the trefoil motif. This is a domain made up almost entirely of 40 amino acids. It’s also known to contain three conserved disulphide bonds. Interestingly, the functions of each trefoil factor are not officially defined. However, it is clear that they all work together to help the epithelium. Primarily, they act to prevent the mucosa from suffering any damage, along with stabilising it. Trefoil factors also serve to directly affect the healing process of the epithelium. TFFs have also been linked to functioning with breast milk. Large amounts of these peptides are found in human milk. It’s discovered that TFF3 activates epithelial cells to create beta-defensins 2 and beta-defensins 4 in breast milk. As a consequence, it can help contribute to the immune system of babies that are breastfed. Trefoil factor 1 is often lost during bouts of gastric carcinoma. It is believed this is down to the mechanism of DNA methylation. Consequently, TFF1 is thought of as a tumour suppressor.

StructureAll members of the trefoil factor family - TFF1, TFF2, and TFF3 - are all found together on chromosome 21, in a close cluster. Trefoil factor 1 and 3 are both characterised by having a singular trefoil domain. Whereas, trefoil factor 2 contains two trefoil domains. Each domain is recognised due to the amino acid residue sequence. You will find 3 disulphide bonds are formed together with 6 cysteines to create a disulphide loop structure that resembles a trefoil or clover shape. Hence the name; trefoil factors. Although TFF1 and TFF3 only have one trefoil domain, they do end up with a 7th cysteine which is free. The reason for this is so the peptide can form dimers using this free cysteine. TFF2 was once known as the Pancreatic Spasmolytic Polypeptide and was the first member of this family to be completely isolated on its own.